Although close to 85% of frail women in long-term care facilities have osteoporosis and the risk of osteoporotic fractures is nearly 10 times that of community dwelling elderly, few are treated and studies are scarce. The potentially potent therapies for osteoporosis in the young may have more risks than benefits in fragile elderly. Furthermore, for the first time we have demonstrated in this frail cohort increases in bone mineral density may not automatically translate to fracture reduction due to compromised skeletal integrity, poor mobility and/or limited life expectancy. Therefore, fracture reduction studies are desperately needed in this vulnerable population. The goal of our proposed R01 is to perform the first fracture reduction clinical trial with a potent antiresorptive agent in the mot vulnerable long-term care population. With our initial R01 we demonstrated the feasibility of recruiting and monitoring, and its efficacy on bone mineral density and bone turnover in a cohort of 180 long-term care residents. However we observed an increase in non-injurious falls. The stage is now set for phase 2, a definitive fracture reduction trial which forms the basis for our R01. We postulate that in frail, institutionalized women an annual infusion of zoledronic acid, an antiresorptive therapy for osteoporosis, will: (H1) be effective demonstrated by fracture reduction; (H2) be safe; and (H3) identify baseline characteristics and concomitant bone structure changes associated with a favorable fracture reduction and bone density response to therapy. To address these hypotheses we will enroll 886 institutionalized women over the age of 65 in a 3 year, randomized, double-blind, calcium and vitamin D controlled trial with the antiresorptive agent zoledronic acid. Use of an intravenous, once yearly agent avoids concerns of oral bisphosphonate side effects, poor absorption and burden on staff. Participants will reside in the long-term care settings associated with the Division of Geriatric Medicine, University of Pittsburgh and will include women with multiple comorbid conditions, functional and cognitive impairment, and limited mobility. Outcome measures will include incident fractures (combined vertebral and nonvertebral), adverse events, safety, bone mineral density, and trabecular bone structure. Novel features include: 1) the first-ever fracture reduction study of a potent antiresorptive agent in the negelected long-term care population, 2) mobile lab for state-of-the-art assessment of vertebral fractures and bone density (safety assessment) on site, 3) an electronic surveillance system to collect adverse events in real time including falls, and 4) exploring the role of bone structure in translating increased BMD to potential fracture reduction. Moreover, we have a unique opportunity to build on our established long-term care intervention infrastructure and track record. This study will provide the necessary data regarding the effectiveness and safety of osteoporosis treatment in elderly, institutionalized women.